Minimal Size of Cell Assemblies Coordinated by Gamma Oscillations

In networks of excitatory and inhibitory neurons with mutual synaptic coupling, specific drive to sub-ensembles of cells often leads to gamma-frequency (25–100 Hz) oscillations. When the number of driven cells is too small, however, the synaptic interactions may not be strong or homogeneous enough to support the mechanism underlying the rhythm. Using a combination of computational simulation and mathematical analysis, we study the breakdown of gamma rhythms as the driven ensembles become too small, or the synaptic interactions become too weak and heterogeneous. Heterogeneities in drives or synaptic strengths play an important role in the breakdown of the rhythms; nonetheless, we find that the analysis of homogeneous networks yields insight into the breakdown of rhythms in heterogeneous networks. In particular, if parameter values are such that in a homogeneous network, it takes several gamma cycles to converge to synchrony, then in a similar, but realistically heterogeneous network, synchrony breaks down altogether. This leads to the surprising conclusion that in a network with realistic heterogeneity, gamma rhythms based on the interaction of excitatory and inhibitory cell populations must arise either rapidly, or not at all. For given synaptic strengths and heterogeneities, there is a (soft) lower bound on the possible number of cells in an ensemble oscillating at gamma frequency, based simply on the requirement that synaptic interactions between the two cell populations be strong enough. This observation suggests explanations for recent experimental results concerning the modulation of gamma oscillations in macaque primary visual cortex by varying spatial stimulus size or attention level, and for our own experimental results, reported here, concerning the optogenetic modulation of gamma oscillations in kainate-activated hippocampal slices. We make specific predictions about the behavior of pyramidal cells and fast-spiking interneurons in these experiments.Collaborative Research in Computational NeuroscienceNational Institutes of Health (U.S.) (grant 1R01 NS067199)National Institutes of Health (U.S.) (grant DMS 0717670)National Institutes of Health (U.S.) (grant 1R01 DA029639)National Institutes of Health (U.S.) (grant 1RC1 MH088182)National Institutes of Health (U.S.) (grant DP2OD002002)Paul G. Allen Family FoundationnGoogle (Firm

Diagnostic Accuracy of 256-Detector Row Computed Tomography in Detection and Characterization of Incidental Pancreatic Cystic Lesions

Purpose. To assess the diagnostic value of 256-detector row MDCT in the characterization of incidentally detected pancreatic cystic lesions (PCLs). Materials and Methods. We retrospectively reviewed 6389 studies performed on a 256-row detector scanner, wherein ≥1 PCLs were incidentally detected. Images from a total of 192 patients (99 females; age range 31–90 years) were analysed referring to morphologic predictive signs of malignancy, including multifocality, inner septa, wall thickening, and mural enhancing nodules. Results. We evaluated 292 PCLs in 192 patients (solitary in 145 and ≥2 in 47; incidence 2.05%). Size ranged from 3 to 145 mm (mean 15 mm); body was the most common location (87/292; 29.8%). Intralesional septa were detected in 52/292 lesions (17.8%), wall thickening >2 mm in 13 (4.5%), enhancing wall and mural nodules in 15 (5.1%) and 12 (4.1%), respectively. Communication with ductal system was evident in 45 cases. The most common diagnoses, established by histology or imaging analysis, were IPMNs (about 86%), while serous cystic neoplasia (3.7%) and metastases (0.5%) were the less common. Conclusion. MDCT provides detailed features for characterization of PCLs, which are incidentally discovered with increased frequency due to the widespread use of cross-sectional imaging

Evidence for Long-Timescale Patterns of Synaptic Inputs in CA1 of Awake Behaving Mice

Repeated sequences of neural activity are a pervasive feature of neural networks in vivo and in vitro. In the hippocampus, sequential firing of many neurons over periods of 100-300 ms reoccurs during behavior and during periods of quiescence. However, it is not known whether the hippocampus produces longer sequences of activity or whether such sequences are restricted to specific network states. Furthermore, whether long repeated patterns of activity are transmitted to single cells downstream is unclear. To answer these questions, we recorded intracellularly from hippocampal CA1 of awake, behaving male mice to examine both subthreshold activity and spiking output in single neurons. In eight of nine recordings, we discovered long (900 ms) reoccurring subthreshold fluctuations or “repeats.” Repeats generally were high-amplitude, nonoscillatory events reoccurring with 10msprecision. Using statistical controls, we determined that repeats occurred more often than would be expected from unstructured network activity (e.g., by chance). Most spikes occurred during a repeat, and when a repeat contained a spike, the spike reoccurred with precision on the order of ≤ 20 ms, showing that long repeated patterns of subthreshold activity are strongly connected to spike output. Unexpectedly, we found that repeats occurred independently of classic hippocampal network states like theta oscillations or sharp-wave ripples. Together, these results reveal surprisingly long patterns of repeated activity in the hippocampal network that occur nonstochastically, are transmitted to single downstream neurons, and strongly shape their output. This suggests that the timescale of information transmission in the hippocampal network is much longer than previously thought. Keywords: hippocampus; intracellular activity; subthreshold patternsNational Institutes of Health (U.S.) (Award 1DP1-NS-087724)National Institutes of Health (U.S.) (Award 1R01-MH-103910

Assembly and operation of the autopatcher for automated intracellular neural recording in vivo

Whole-cell patch clamping in vivo is an important neuroscience technique that uniquely provides access to both suprathreshold spiking and subthreshold synaptic events of single neurons in the brain. This article describes how to set up and use the autopatcher, which is a robot for automatically obtaining high-yield and high-quality whole-cell patch clamp recordings in vivo. By following this protocol, a functional experimental rig for automated whole-cell patch clamping can be set up in 1 week. High-quality surgical preparation of mice takes ~1 h, and each autopatching experiment can be carried out over periods lasting several hours. Autopatching should enable in vivo intracellular investigations to be accessible by a substantial number of neuroscience laboratories, and it enables labs that are already doing in vivo patch clamping to scale up their efforts by reducing training time for new lab members and increasing experimental durations by handling mentally intensive tasks automatically.National Eye InstituteNational Institute of Mental Health (U.S.) (1-U01-MH106027-01)United States. National Institutes of Health (EY023173)National Science Foundation (U.S.) (HER 0965945)National Science Foundation (U.S.) (CISE 1110947)National Science Foundation (U.S.) (5T90DA032466)Georgia Institute of TechnologyUnited States. National Institutes of Health (1R01EY023173)New York Stem Cell Foundation (Robertson Neuroscience Investigator Award)United States. National Institutes of Health (1DP1NS087724)United States. National Institutes of Health (1R24MH106075)United States. National Institutes of Health (1R01MH103910